Iliopsoas Release for Internal Snapping Hip using a Minimally Open Medial Hip Approach-Case Report

Internal snapping hip is a recognized cause of hip pain caused by recurrent subluxation of the iliopsoas tendon. When conservative treatment fails, surgical release of the iliopsoas tendon may be indicated using an arthroscopic or open hip approach. Results have been better with arthroscopic release. We report a case of a 32-year-old active female with a painful internal snapping hip. The right hip extension from a flexed position produced a strong and audible snap. A tenotomy of the iliopsoas in combination with a resection of the lesser trochanter was performed, using a limited medial hip approach different than the one described by Ludloff or Ferguson. The pain and snapping phenomenon were solved; however, a slight heterotopic ossification, as well as a weakness in the flexion of the hip was noted after the procedure, with no functional limitation. The minimally invasive medial hip approach appears to be a simple, reproducible and successful operation for the treatment of an internal snapping hip caused by the iliopsoas tendon, namely in orthopaedics departments with limited experience in hip arthroscopic approach, but it is not superior to arthroscopic release.info:eu-repo/semantics/publishedVersio

Development of TNBS-induced colitis: animal model to test new pharmacological approaches

IBD is a gastro-intestinal disorder marked with chronic inflammation of intestinal epithelium, dam- aging mucosal tissue and manifests into several intestinal and extra-intestinal symptoms. Currently used medical therapy is able to induce and maintain the patient in remission, however no modifies or reverses the underlying pathogenic mechanism. The research of other medical approaches is crucial to the treatment of IBD and, for this, it ́s important to use animal models to mimic the characteristics of disease in real life. The aim of the study is to develop an animal model of TNBS-induced colitis to test new pharmacological approaches. TNBS was instilled intracolonic single dose as described by Morris et al. It was administered 2,5% TNBS in 50% ethanol through a catheter carefully inserted into the colon. Mice were kept in a Tredelenburg position to avoid reflux. On day 4 and 7, the animals were sacrificed by cervical dislocation. The induction was confirmed based on clinical symptoms/signs, ALP determination and histopathological analysis. At day 4, TNBS group presented a decreased body weight and an alteration of intestinal motility characterized by diarrhea, severe edema of the anus and moderate morbidity, while in the two control groups weren’t identified any alteration on the clinical symptoms/signs with an increase of the body weight. TNBS group presented the highest concentrations of ALP comparing with control groups. The histopathology analysis revealed severe necrosis of the mucosa with widespread necrosis of the intestinal glands. Severe hemorrhagic and purulent exsudates were observed in the submucosa, muscular and serosa. TNBS group presented clinical symptoms/ signs and histopathological features compatible with a correct induction of UC. The peak of manifestations became maximal at day 4 after induction. This study allows concluding that it’s possible to develop a TNBS- induced colitis 4 days after instillation. DII é um distúrbio gastro-intestinal caracterizado por inflamação crónica do epitélio intestinal com dano associado da mucosa, manifestando-se a partir de sintomas intestinais e extra-intestinais. A terapia médica utilizada é capaz de induzir e manter o doente em remissão, mas não modifica ou inverte o mecanismo patogénico subjacente. A procura de outras abordagens terapêuticas é crucial para o tratamento de DII e, para tal, é importante o uso de modelos animais para mimetizar as características da doença. O objetivo do estudo é desenvolver um modelo animal de colite induzida por TNBS de modo a testar novas abordagens farmacológicas. O TNBS foi instilado por via intracolónica em dose única como descrito por Morris et al. Foi administrado 2,5% de TNBS em 50% de etanol através de um cateter inserido no cólon. Os animais foram mantidos em posição Tredelenburg para evitar o refluxo. Nos dias 4 e 7, os animais foram sacrificados por deslocamento cervical. A indução de colite foi caracterizada com base nos sintomas/sinais clínicos, determinação de ALP e análise histopatológica. No dia 4, o grupo TNBS apresentou uma diminuição do peso corporal e uma alteração da motilidade intestinal caracterizada por diarreia, edema severo do ânus e morbilidade moderada, enquanto nos dois grupos controlo não foram identificados quaisquer alterações nos sintomas/ sinais clínicos com um aumento do peso corporal. O grupo TNBS apresentou as maiores concentrações de ALP, comparando com os grupos controlo. A análise histopatológica demonstrou necrose grave da mucosa com necrose generalizada das glândulas intestinais. Foi observado exsudato hemorrágico e purulento ao nível da submucosa, muscular e serosa. O grupo TNBS apresentou sintomas / sinais clínicos e características histopatológicas compatíveis com uma correta indução de colite. O pico das manifestações tornou-se máximo ao 4º dia após a indução. Este estudo permite concluir que é possível desenvolver colite induzida por TNBS 4 dias após a instilação.

Pathways to folding, nucleation events and native geometry

We perform extensive Monte Carlo simulations of a lattice model and the Go potential to investigate the existence of folding pathways at the level of contact cluster formation for two native structures with markedly different geometries. Our analysis of folding pathways revealed a common underlying folding mechanism, based on nucleation phenomena, for both protein models. However, folding to the more complex geometry (i.e. that with more non-local contacts) is driven by a folding nucleus whose geometric traits more closely resemble those of the native fold. For this geometry folding is clearly a more cooperative process.Comment: Accepted in J. Chem. Phy

Stereological Estimation of Mean Nuclear Volume as a Prognostic Factor in Canine Mast Cell Tumors

Cutaneous mast cell tumour (MCT) Patnaik and Kiupel grading schemes rely on qualitative and semiquantitative features susceptible to interobserver variability. Stereological estimation of volume-weighted mean nuclear volume (MNV) provides information about both size and variability of nuclear size, which has been proven to have a prognostic value in other solid tumours. The objective was to compare MNV with MCT grade and biological behaviour. Fifty-six MCTs were graded according to Patnaik and Kiupel by consensus of three experienced pathologists.Clinical history of dogs treated with surgical excision alone was collected with a minimum follow-up period of 1 year (n=31).MNV was estimated using the point-intercept method on vertical sections in 10 microscopical fields, with an approximately constant distance proportional to overall sectional area. Animals were divided according to outcome: group 1, no recurrence; group 2, local recurrence, lymph node or distant metastasis. The present study suggests that estimation of MNV on routine histological sections may objectively improve the detection of more aggressive MCTs

Gla-rich protein (GRP) as an early and novel marker of vascular calcification and kidney dysfunction in diabetic patients with CKD: a pilot cross-sectional study

Vascular calcification (VC) is one of the strongest predictors of cardiovascular risk in chronic kidney disease (CKD) patients. New diagnostic/prognostic tools are required for early detection of VC allowing interventional strategies. Gla-rich protein (GRP) is a cardiovascular calcification inhibitor, whose clinical utility is here highlighted. The present study explores, for the first time, correlations between levels of GRP in serum with CKD developmental stage, mineral metabolism markers, VC and pulse pressure (PP), in a cohort of 80 diabetic patients with mild to moderate CKD (stages 2-4). Spearman's correlation analysis revealed a positive association of GRP serum levels with estimated glomerular filtration rate (eGFR) and α-Klotho, while a negative correlation with phosphate (P), fibroblast growth factor 23 (FGF-23), vascular calcification score (VCS), PP, calcium (x) phosphate (CaxP) and interleukin 6 (IL-6). Serum GRP levels were found to progressively decrease from stage 2 to stage 4 CKD. Multivariate analysis identified low levels of eGFR and GRP, and high levels of FGF-23 associated with both the VCS and PP. These results indicate an association between GRP, renal dysfunction and CKD-mineral and bone disorder. The relationship between low levels of GRP and vascular calcifications suggests a future, potential utility for GRP as an early marker of vascular damage in CKD.Portuguese Society of Nephrology (SPN) ; Portuguese national funds from FCT-Foundation for Science and Technology through the transitional provision DL57/2016/CP1361/CT0006 UIDB/04326/2020info:eu-repo/semantics/publishedVersio

Gold nanoparticles as a part of a photothermal therapy system.

Introduction Photothermal therapy (PTT) is attracting increased attention for the treatment of superficial localized tumors, relying on the induction of local hyperthermia of tumor cells upon their irradiation with light beams1. PTT efficacy depends, however, on the heat generated and, on the depth reached by the light. Some strategies to improve PTT efficacy includes the use of the near infrared (NIR, 650 to 900 nm) radiation to enhance the penetration depth of the light, combined with gold nanoparticles (AuNPs) to enhance the photothermal effect2. Experimental Methods Core AuNPs were synthesized by a novel method using tetrachloroauric acid and a mixture of reducing agents, and subsequently coated with a combination of hyaluronic and oleic acids, for improving the NPs biocompatibility, biodegradability, and lifetime. This coating also promotes the binding of specific cell receptors of the tumor cells. The particles were physico-chemically characterized, and in vitro and in vivo tests were carried out in breast cancer models to assess their safety and efficacy, when applied alone or combined with NIR irradiation3. Results and Discussion AuNPs presented a predominant spherical morphology with sizes under 350 nm, polydispersity index lower than 0.4 and enhanced absorbance in the NIR. The particles showed no toxicity in vitro and promising efficacy in vivo when administering the NPs in situ and later irradiating them externally. Histopathological analysis of tumors treated with both AuNPs and laser irradiation showed the presence of necrosis in most of the tumors and no effect or practically absence in healthy surrounding cells, which are very encouraging outcomes. Conclusion The results are promising, however, there is still room for improving the system, namely by reducing even more the invasiveness of the treatment through the combined use of aerogels structures. Aerogel’s unique properties4 make them ideal candidates to minimize the exposure of healthy tissues to laser radiation, acting as light and thermal insulators, as well as to incorporate the nanoparticles into their skeletal structure and thus potentiating a topical application of the particles. For these reasons, some exploratory methods were carried to produce and design aerogels structures for PTT applications

Gla-Rich protein, magnesium and phosphate associate with mitral and aortic valves calcification in Didabetic patients with moderate CKD

Accelerated and premature cardiovascular calcification is a hallmark of chronic kidney disease (CKD) patients. Valvular calcification (VC) is a critical indicator of cardiovascular disease and all-cause mortality in this population, lacking validated biomarkers for early diagnosis. Gla-rich protein (GRP) is a cardiovascular calcification inhibitor recently associated with vascular calcification, pulse pressure, mineral metabolism markers and kidney function. Here, we examined the association between GRP serum levels and mitral and aortic valves calcification in a cohort of 80 diabetic patients with CKD stages 2–4. Mitral and aortic valves calcification were detected in 36.2% and 34.4% of the patients and associated with lower GRP levels, even after adjustments for age and gender. In this pilot study, univariate, multivariate and Poisson regression analysis, show that low levels of GRP and magnesium (Mg), and high levels of phosphate (P) are associated with mitral and aortic valves calcification. Receiver operating characteristic (ROC) curves showed that the area under the curve (AUC) values of GRP for mitral (0.762) and aortic (0.802) valves calcification were higher than those of Mg and P. These results suggest that low levels of GRP and Mg, and high levels of P, are independent and cumulative risk factors for VC in this population; the GRP diagnostic value might be potentially useful in cardiovascular risk assessment.info:eu-repo/semantics/publishedVersio

The folding of knotted proteins: insights from lattice simulations

We carry out systematic Monte Carlo simulations of Go lattice proteins to investigate and compare the folding processes of two model proteins whose native structures differ from each other due to the presence of a trefoil knot located near the terminus of one of the protein chains. We show that the folding time of the knotted fold is larger than that of the unknotted protein and that this difference in folding time is particularly striking in the temperature region below the optimal folding temperature. Both proteins display similar folding transition temperatures, which is indicative of similar thermal stabilities. By using the folding probability reaction coordinate as an estimator of folding progression we have found out that the formation of the knot is mainly a late folding event in our shallow knot system

A Step Forward in Breast Cancer Research: From a Natural-Like Experimental Model to a Preliminary Photothermal Approach

Supplementary Materials - The following are available online at https://www.mdpi.com/1422-0067/21/24/9681/s1, Figure S1: GNPs’ size distribution by intensity (%) obtained by DLS.Breast cancer is one of the most frequently diagnosed malignancies and common causes of cancer death in women. Recent studies suggest that environmental exposures to certain chemicals, such as 7,12-Dimethylbenzanthracene (DMBA), a chemical present in tobacco, may increase the risk of developing breast cancer later in life. The first-line treatments for breast cancer (surgery, chemotherapy or a combination of both) are generally invasive and frequently associated with severe side effects and high comorbidity. Consequently, novel approaches are strongly required to find more natural-like experimental models that better reflect the tumors’ etiology, physiopathology and response to treatments, as well as to find more targeted, efficient and minimally invasive treatments. This study proposes the development and an in deep biological characterization of an experimental model using DMBA-tumor-induction in Sprague-Dawley female rats. Moreover, a photothermal therapy approach using a near-infrared laser coupled with gold nanoparticles was preliminarily assessed. The gold nanoparticles were functionalized with Epidermal Growth Factor, and their physicochemical properties and in vitro effects were characterized. DMBA proved to be a very good and selective inductor of breast cancer, with 100% incidence and inducing an average of 4.7 tumors per animal. Epigenetic analysis showed that tumors classified with worst prognosis were hypomethylated. The tumor-induced rats were then subjected to a preliminary treatment using functionalized gold nanoparticles and its activation by laser (650–900 nm). The treatment outcomes presented very promising alterations in terms of tumor histology, confirming the presence of necrosis in most of the cases. Although this study revealed encouraging results as a breast cancer therapy, it is important to define tumor eligibility and specific efficiency criteria to further assess its application in breast cancer treatment on other species.The APC was funded by Faculty of Pharmacy, University of Coimbra and Coimbra Chemistry Centre, Department of Chemistry, University of Coimbra. This work was also supported by Fundação para a Ciência e Tecnologia (FCT), Portugal under the project’s references UIDB/00645/2020 and UID/DTP/04138/2019. TFG was supported by FCT, Portugal under the reference SFRH/BD/147306/2019. Thanks to FCT/MCTES for the financial support to CESAM (UIDP/50017/2020+UIDB/50017/2020), through national funds.info:eu-repo/semantics/publishedVersio

Folding of small proteins: A matter of geometry?

We review some of our recent results obtained within the scope of simple lattice models and Monte Carlo simulations that illustrate the role of native geometry in the folding kinetics of two state folders.Comment: To appear in Molecular Physic